title: Chemical-protein interactome and its application in off-target identification.
abstract: Drugs exert their therapeutic and adverse effects by interacting with molecular targets. Although designed to interact with specific targets in a desirable manner, drug molecules often bind to unexpected proteins (off-targets). By activating or inhibiting off-targets and the associated biological processes and pathways, the resulting chemical-protein interactions can influence drug reaction directly or indirectly. Exploring the relationship between drug and off-targets and the downstream drug reaction can help understand the polypharmacology of the drug, hence significantly advance the drug repositioning pipeline and the application of personalized medicine in understanding and preventing adverse drug reaction. This review summarizes works on predicting off-targets via chemical-protein interactome (CPI), an interaction strength matrix of drugs across multiple human proteins aiming at exploring the unexpected drug-protein interactions, with a variety of computational strategies, including docking, chemical structure comparison and text-mining etc. Effective recall on previous knowledge, de novo prediction and subsequent experimental validation conferred us strong confidence in these methods. Such studies present prospect of large scale in silico methodologies for off-target discovery with low cost and high efficiency.
authors.affiliation: Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, 200030, China. lun.yang@gmail.com
authors.forename: Lun
authors.initials: L
authors.lastname: Yang
authors.forename: Ke-Jian
authors.initials: KJ
authors.lastname: Wang
authors.forename: Li-Shan
authors.initials: LS
authors.lastname: Wang
authors.forename: Anil G
authors.initials: AG
authors.lastname: Jegga
authors.forename: Sheng-Ying
authors.initials: SY
authors.lastname: Qin
authors.forename: Guang
authors.initials: G
authors.lastname: He
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Yue
authors.initials: Y
authors.lastname: Xiao
authors.forename: Lin
authors.initials: L
authors.lastname: He
mesh_terms: D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D030562:Databases, Protein; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D054730:Protein Interaction Domains and Motifs; D011506:Proteins / Q000737:chemistry*; D013678:Technology, Pharmaceutical
chemical_list: D004364:Pharmaceutical Preparations; D011506:Proteins